Dr Hasan Chowhan (left) and Valerie Pentney explain how the NICE quality standard for hepatitis B helps to improve access to diagnosis, vaccination, and care to reduce disease burden

 
  • Remain alert to people you encounter who are at risk of HBV infection, and perform testing:
  • a new patient registration check could present the ideal opportunity for initial discussions
  • Have processes in place to provide vaccination for people requiring it
  • Stress the importance of antenatal screening for pregnant women:
  • the transfer of care between maternity services and primary care can be a key issue and effective coordination and communication between services is important
  • When children are born to HBsAg-positive mothers, help reinforce the message to complete the child’s vaccination course
     
  • Speak to the local gastroenterologists/hepatologists to agree referral pathways and monitoring of infected patients
     
  • Agree laboratory tests and interpretation with the microbiology unit
     
  • Advertise the risks of undiagnosed HBV in your surgery, especially at antenatal and genito-urinary medicine clinics
     
  • Engage with community organisations and charities to target hard-to-reach groups with education about HBV and its associated risks
     
  • Make transition from children’s services to adult services as seamless as possible for patients.
HBV=hepatitis B; HBsAg=hepatitis B surface antigen
Hepatitis B (HBV) is a viral infection of the liver that can present as an acute or chronic infection. Acute infections can cause abdominal pain, nausea, malaise, and jaundice and can progress into a chronic infection, associated with chronic liver disease and hepatocellular carcinoma (HCC). About 85% of HBV infections in newborn babies become chronic, compared with 4% in adults.1 Hepatitis B can be transmitted through contact with blood or bodily fluids or vertically from mother to child perinatally.

Diagnosis and classification

Acute or chronic HBV is characterised by the presence of detectable hepatitis B surface antigen (HBsAg), a viral protein, in the blood or serum. The progression of liver disease is usually assessed with HBV DNA levels in the blood or ‘viral load’, which is an indicator of viral replication. Higher HBV DNA levels are usually associated with an increased risk of liver disease and HCC. Hepatitis B DNA levels typically fall in response to effective antiviral treatment,2 preventing or decreasing hepatic inflammation and fibrosis, cirrhosis, HCC, and liver failure.

Classification of chronic HBV is through the presence or absence of the e-antigen (HBeAg), i.e. HBeAg positive or HBeAg negative. The presence of HBeAg is typically associated with higher rates of viral replication, and therefore increased infectivity.1 In clinical practice, surrogate markers are used to monitor progression of disease and treatment response, including:2

  • normalisation of serum alanine aminotransferase (ALT) levels
  • decrease in inflammation scores with no worsening or improvement in fibrosis on liver biopsies
  • suppression of serum HBV DNA to undetectable levels
  • loss of HBeAg and seroconversion to HBe antibody (anti-HBe)
  • loss of HBsAg and seroconversion to HBs antibody (anti-HBs).

Many effective and safe treatments exist, including interferon alfa. Several nucleoside and nucleotide analogues are approved for use in adults with chronic HBV, together with a pegylated form of interferon alfa.2 Questions remain about the timing, sequence, and combination of medication, and about which patients can be monitored 6-monthly with delayed treatment.

Prevalence and incidence

Reported acute HBV per 100,000 people in England in 2013 was 0.77, a reduction from 1.04 in 2012, and 1.13 in 2011.3 There is ambiguity over chronic HBV prevalence in the UK: the Department of Health suggests that 180,000 people are infected, whereas Hepatitis B Foundation UK implies the number could be closer to 326,000.4

It is estimated that HBV is responsible for 50%–80% of HCC cases worldwide.5 During a research study in China, with all male participants, there was an annual incidence rate of HCC in HBsAg carriers of 494 per 100,000, compared with 5 per 100,000 in HBsAg-negative men, and chronic HBV infection is associated with a 98-fold higher relative risk for HCC.6

In 2002, GLOBOCAN global analysis estimated that 82% of liver cancer cases (and deaths) occurred in developing countries, 55% in China alone.7 Areas where the incidence of liver cancer is moderately high (11–20 cases per 100,000 male inhabitants) or very high (20 per 100,000) include China, south eastern Asia, and sub-Saharan western and eastern Africa;8 however, these are cases of liver cancer from all causes, not just those resulting from HBV. 

Immigration statistics for the UK during 2013–2014 report an increase of 10% in work-related visas and 7% in study-related visas, with higher numbers of applications from Chinese, Brazilian, Malaysian, and Libyan nationals compared with the year before.9 The reduction of acute  Hepatitis B can be prevented by vaccination; immunisation is used for individuals at high risk of exposure or complications of the disease (e.g. people who inject drugs, and healthcare workers). Immediate post-exposure vaccination is used to prevent infection, especially in babies born to infected mothers or following needle-stick injuries.10 Hepatitis B vaccination programmes were initiated in many East Asian and Asia-Pacific countries during the late 1980s11,12 and have begun to reduce mother-to-infant transmission, which is the key factor driving chronic HBV infection.13

The need for a quality standard

NICE Quality Standard 65 (QS65) on Hepatitis B (see www.nice.org.uk/guidance/qs65) encompasses guidance for newborn babies, young people, and adults, and promotes quality improvement for the testing, diagnosis, and management of HBV for the whole population.2 In providing a well-defined narrative for a high quality, gold standard service for people with HBV (see Table 1, below), NICE QS65 contributes to the Department of Health NHS14 and public health15 outcomes frameworks for England by targeting the following outcomes, overarching indicators, and areas of required improvement:14,15

  • NHS outcomes framework domains 1 and 2:
  • preventing people from dying prematurely
  • enhancing quality of life for people with long-term conditions
  • public health outcomes framework domain 4:
  • healthcare, public health, and preventing premature mortality.

By using QS65 in conjunction with, for example, the NICE Hepatitis B (chronic) pathways,16 organisations and practitioners can ensure that people are supported to understand, access, and receive treatment and care in order to reduce morbidity and mortality. All the quality statements are auditable, allowing benchmarking with equality and diversity considerations throughout.

This quality standard, if fully implemented, should indicate improvements in the following outcomes:2

  • mortality from liver disease attributable to HBV
  • vertical transmission from HBC surface antigen (HBsAg)-positive mother to child: and babies identified as being HBV-positive after 1 year
  • people being able to live better with the condition.

 

Table 1: NICE quality standard for hepatitis B (QS65)2
No.Quality Statement
1 People who are at increased risk of hepatitis B infection are offered testing and vaccination.
2 People who test positive for hepatitis B surface antigen (HBsAg) are referred to specialist care for further assessment.
3 Pregnant women who are identified as hepatitis B surface antigen (HBsAg)-positive at antenatal screening are assessed by a specialist within 6 weeks of receiving the screening test result.
4 Babies born to hepatitis B surface antigen (HBsAg)-positive mothers receive a complete course of hepatitis B vaccination and, at age 12 months, receive a blood test for hepatitis B infection.
5 People with chronic hepatitis B infection, and their family members or carers (if appropriate), are offered a personalised care plan outlining the proposed treatment and long-term management of their infection.
6 People with chronic hepatitis B infection who do not meet the criteria for antiviral treatment are monitored regularly at intervals determined by their infection status and age.
7 Adults with chronic hepatitis B infection who have significant liver fibrosis or cirrhosis are offered 6-monthly surveillance testing for hepatocellular carcinoma.
NICE (2014). Quality Standard 65. Hepatitis B. Available at: www.nice.org.uk/guidance/QS65 Reproduced with permission.

Testing and vaccination—statement 1

Estimated figures for the incidence of chronic HBV suggest that it may be underdiagnosed in the UK.2  Implementation of NICE QS65 statement 1 is essential in order to find infected people early, diagnose them promptly, and offer them effective treatments to prevent their disease from progressing. The statement will also help to protect people who may unknowingly be putting themselves at risk of infection with HBV. It is important that healthcare practitioners have discussions with people both before and after testing or vaccination to ensure they understand their risk of infection, and that practitioners offer counselling if a person is found to be infected.2

 

Referral for specialist care—statement2

Undiagnosed and untreated chronic HBV can cause liver disease and other serious health problems; infected people can also be at risk from HIV, hepatitis C, and hepatitis D.2 Primary care clinicians should refer to NICE Clinical Guideline (CG) 165 on Hepatitis B (chronic): Diagnosis and management of chronic hepatitis B in children, young people and adults, recommendation 1.2 for further recommended pathology tests before referral (see www.nice.org.uk/guidance/cg165/chapter/1-recommendations).17 It is important that people who test positive for HBsAg are referred for specialist care to allow diagnosis of the stage of HBV. For a definition of ‘specialist care’, see NICE CG165 and QS65.2,17

For patients, carers, and service users, this quality statement reinforces the need to ensure that local referral pathways are in place. Processes for contact-tracing for the purpose of testing and vaccination will be required.

Pregnant women

Statement 1 does not apply to pregnant women. Further assessment is essential in determining whether and when to start pharmacological treatment10 for pregnant women who test HBsAg positive at antenatal screening, for whom quality statement 3 will apply.

 

Referral and assessment for pregnant women identified as HBsAg positive at antenatal screening—statement3

Given the risk of vertical transmission from mother to child, this quality statement is important in preventing the spread of HBV; referring the mother within 6 weeks of receiving the screening test result will allow antiviral treatment (tenofovir) to be given to the mother in the third trimester, if needed, to reduce the risk of the baby becoming infected with HBV.10 
 
UK guidelines (Department of Health, 1998)18 recommend that all pregnant women should be offered screening for hepatitis B infection during each pregnancy, which will enable screening for new infections between pregnancies.
 

The importance of antenatal screening should be stressed to all expectant mothers, particularly to local migrant populations who come from an area of high HBV prevalence. Special consideration should also be given to groups of women with complex social needs, e.g. those with a history of substance misuse (alcohol and/or drugs), difficulties speaking English, who are aged under 20 years, or who live in poverty or are homeless.2 Provision of antenatal care should be integrated into the maternity pathway, ensuring a coordinated approach from all providers for high quality, seamless care to pregnant women.

Neonatal hepatitis B vaccination and blood testing at 12 months—statement 4

Hepatitis B can be transmitted to babies born to HBsAg-positive mothers at or around the time of birth. Babies who acquire the infection have a very high risk of developing chronic HBV, and vaccinating babies is highly effective at preventing perinatal transmission.2,10 The first vaccine should be given to the baby at birth (see below) and the recommended vaccination course given at the right time, including, when appropriate, HBV immunoglobulin, in line with PHE guidance.10,17 A complete course consists of an initial dose of vaccine within 24 hours of birth—and of HBV immunoglobulin (HBIG) for babies born to highly infectious mothers, administered at a different site to the vaccine—with further doses of vaccine at 1 month, 2 months, and 12 months, plus an additional booster at preschool age.10 A blood test for HBsAg should be performed when the baby is 12 months old (i.e. at the time of the fourth dose) to check for vaccine failure. Where immunisation has been delayed beyond the recommended intervals, the vaccine course should be completed, but it is more likely that the child may become infected. In this instance, testing for HBsAg above the age of 1 year is particularly important.10
 
During 2012–2013, 89% of those babies born to HBsAg-positive mothers were immunised for HBV by their first birthday and 79% by their second birthday.19 These figures indicate that not all children complete the vaccination course. Non-compliance with the full course of vaccination will result in an increased risk of the child becoming infected. Part of the issue here is educating patients but also, commissioners need to have appropriate processes in place, for example a clear pathway, coordinated vaccination programme (including scheduling and follow up to ensure babies at risk are vaccinated at the right time), and a blood test at age 12 months to test for HBsAg.

Personalised care plan—statement 5

All care plans should be produced within secondary care as this is the site of specialist knowledge. Care plans should be designed around the individual and encourage patient engagement, compliance with treatment, and self-awareness of risk; this should help to minimise non-attendance, inadequate monitoring, and poor outcomes.2 People should be aware that HBV is often a lifelong, asymptomatic condition that requires long-term treatment and they should understand how to manage their illness. Care plans can be created with the involvement of healthcare professionals, carers, or family members so as to promote discussion and full contribution to decision-making. People with HBV should be encouraged to follow their care plan and to take an active role in ensuring that any necessary monitoring, treatment, and/or screening tests happen in a timely way.2
 

For patients diagnosed in childhood, it is imperative that their care plan flows with them into adulthood and when adult services are introduced. Commissioners and healthcare professionals need to ensure that the transition from children’s services to adult services is as seamless as possible for these patients.

Monitoring—statement 6

This statement applies to people with chronic infection only, defined in the quality standard as the persistence of HBsAg for 6 months or more after acute infection with HBV (HBeAg-positive or HBeAg-negative) disease. Monitoring should commence promptly after diagnosis. For people not taking antiviral medication, continuous follow up and review of the care plan should take place, establishing the stage of infection, whether treatment should begin, and if they are at risk of developing fibrosis.

People who may not be receiving antiviral treatment but who will require close monitoring include children and young people, adults with HBeAg-positive disease in the immune-tolerant and immune-clearance phases, and adults with inactive chronic hepatitis B infection.16 It is essential that practitioners do not lose touch with these patients. It may be that they come from ‘hard-to-reach groups’ so GPs need to agree local strategies and involve community organisations and charities to assist.

Six-monthly surveillance testing for hepatocellular carcinoma—statement 7

Hepatocellular carcinoma is the fifth most common neoplasm worldwide.8 Its very poor prognosis makes it the third leading global cause of cancer-related mortality, responsible for 600,000 deaths annually.8 Liver disease is the fifth largest cause of death in the UK.20 Direct healthcare costs, currently in excess of £0.5bn per annum, are rising by 10% per year and are expected to be £1bn per annum by 2015.21 In most countries, HCC accounts for 70%–85% of primary liver cancer cases.22 Given the progression of significant liver fibrosis or cirrhosis into primary liver cancer, it is crucial that these patients are monitored.

Equality and diversity

NICE QS65 explains in detail equality and diversity considerations. For example, the development of a personalised care plan should be consistent with cultural and religious beliefs and tailored to the individual.14  Because of the incidence rate of HBV in developing countries and immigration into the UK, it is important that consideration is given to the formats of patient education, ensuring that these are available in different languages. Testing and vaccination should also be offered in a variety of locations and settings, allowing exposure to different age groups and cultures at increased risk.

Conclusion

Hepatitis B appears to be a treatable disease, and we now have the opportunity to reduce its burden on the healthcare system. To do this, we need to be able to engage more with our communities and with healthcare staff to help communicate the message. Commissioners can help by implementing this quality standard. Clinical guidelines and the NICE quality standard together give us the framework to tackle HBV comprehensively, but we will need the support of all the relevant stakeholders.

Box 1: Useful resources for implementing NICE QS65 for hepatitis B2

NICE resources

Public Health England resources

Department of Health resources 

Royal College of General Practitioners

 
  • This quality standard is likely to require intervention by CCGs, NHS England (for specialist commissioning), and local public health departments:
  • the above three agencies should consider a local but coordinated response to it
  • Public health departments have a key role in:
  • identifying groups of patients likely to be at high risk of hepatitis B (e.g. immigrant populations)
  • promoting awareness and testing for hepatitis B through primary care and sexual health clinics
  • Antenatal patients are a key group for identification of hepatitis B. Clinical commissioning groups and public health departments should:
  • review their local antenatal screening procedures and take-up rates, and seek to improve screening rates
  • ensure that there is a care pathway in place, allowing rapid specialist assessment for HBsAg-positive mothers, anti-viral treatment and neonatal vaccination
  • Clinical commissioning groups, in liaison with specialist commissioning colleagues, should ensure that they have commissioned services in line with the quality standard to ensure the correct follow up and specialist care for people diagnosed with chronic hepatitis B infection, to help prevent liver cancer and mortality.
CCG=clinical commissioning group; HBsAg=hepatitis B surface antigen
  1. NICE. Hepatitis B and C: ways to promote and offer testing to people at increased risk of infection. NICE Public Health Guidance 43. London: NICE, 2012. Available at www.nice.org.uk/guidance/PH43
  2. NICE website. Hepatitis B. Quality Standard 65. www.nice.org.uk/guidance/QS65 (accessed 25 September 2014)
  3. Public Health England. Infection Reports: Immunisation: Acute hepatitis B (England); annual report for 2013. Health Protection Report Vol. 8 No.33. London: Public Health England, 2014. Available at: www.gov.uk/government/uploads/system/uploads/attachment_data/file/348576/hpr3314_hbv13.pdf
  4. Hepatitis UK Foundation. Home page. www.hepb.org.uk/ (accessed 29 September 2014).
  5. Ahmed F, Perz J, Kwong S et al. National trends and disparities in the incidence of hepatocellular carcinoma, 1998–2003. Prev Chronic Dis 2008; 5 (3): A74.
  6. Venook A, Papandreou C, Furuse J, Ladrón de Guevara L. The incidence and epidemiology of hepatocellular carcinoma: A global and regional perspective. Oncologist 2010; 15 Suppl 4: 5–13.
  7. Parkin D, Bray F, Ferlay J et al. Global cancer statistics, 2002. CA Cancer J Clin 2005; 55 (2): 74–108. 
  8. Gomaa A, Khan S, Toledano M et al. Hepatocellular carcinoma: Epidemiology, risk factors and pathogenesis. World J Gastroenterol 2008; 14 (27): 4300–4308.
  9. Home Office. Statistical News Release: Immigration Statistics, April–June 2014. London: Home Office, 2014. Available at www.gov.uk/government/uploads/system/uploads/attachment_data/file/347878/immigration-q2-2014snr.pdf
  10. Department of Health. Immunisation against infectious disease (‘the green book’). London: Department of Health, 2006. Available at: www.gov.uk/government/publications/hepatitis-b-the-green-book-chapter-18
  11. Yuen M, Hou J, Chutaputti A. Asia Pacific Working party on prevention of hepatocellular carcinoma. Hepatocellular carcinoma in the Asia Pacific region. J Gastroenterol Hepatol 2009; 24 (3): 346–353.  
  12. Hsu H, Chen D, Chuang C et al. Efficacy of a mass hepatitis B vaccination program in Taiwan. Studies on 3464 infants of hepatitis B surface antigen-carrier mothers. JAMA 1988; 260 (15): 2231–2235.
  13. Beasley R. Rocks along the road to the control of HBV and HCC. Ann Epidemiol 2009; 19 (4): 231–234.
  14. Department of Health. NHS outcomes framework 2014–2015. Available at: www.england.nhs.uk/resources/resources-for-ccgs/out-frwrk/ (accessed 29 September 2014). 
  15. Department of Health. Public health outcomes framework 2013–2016. Healthy lives, healthy people: Improving outcomes and supporting transparency. Available at: www.phoutcomes.info (accessed 29 September 2014).
  16. NICE website. Hepatitis B (chronic) pathway. pathways.nice.org.uk/pathways/hepatitis-b-chronic (accessed 29 September 2014).
  17. NICE. Hepatitis B (chronic): diagnosis and management of chronic hepatitis B in children, young people and adults. NICE Clinical Guideline 165. NICE, 2013. Available at:
  18. Department of Health. Screening of pregnant women for hepatitis B and immunisation of babies at risk. Health Service Circular HSC 1998/127. London, 2008. Available at: www.dh.gov.uk/assetRoot/04/01/18/40/04011840.pdf
  19. Health and Social Care Information Centre. NHS Immunisation Statistics, England—2012–13 [NS]. London: Health and Social Care Information Centre, 2013. Available at: www.hscic.gov.uk/searchcatalogue?productid=12410&q=Hepatitis+B&topics=0%2fPublic+health&sort=Relevance&size=10&page=1#top
  20. British Association for the Study of the Liver (BASL) & British Society of Gastroenterology (BSG). National plan for liver services UK 2009. London: British Society of Gastroenterology, 2009. Available at: www.bsg.org.uk/sections/liver-articles/the-national-plan-for-liver-services-uk-2009.html
  21. Lombard M. Hepatitis C and offender health. London: DH, 2011. Available at: webarchive.nationalarchives.gov.uk/20130502170157/http://www.hpa.org.uk/webc/HPAwebFile/HPAweb_C/1317136324683
  22. Ahmed F, Perz J, Kwong S et al. National trends and disparities in the incidence of hepatocellular carcinoma, 1998–2003. Prev Chronic Dis 2008; 5 (3): A74.
  23. NICE website. Pathway for hepatitis B and C testing. pathways.nice.org.uk/pathways/hepatitis-b-and-c-testing (accessed 25 September 2014).
  24. NICE website. Immunisation for children and young people: overview. pathways.nice.org.uk/pathways/immunisation-for-children-and-young-people (accessed 25 September 2014).
  25. NICE website. Pathway for implementing the hepatitis B immunisation programme for infants born to hepatitis B-positive mothers.
    bit.ly/NICE-HepBPathway-infants (accessed 25 September 2014).
  26. NICE. Reducing differences in the uptake of immunisations. NICE Public Health Guidance 21. London: NICE, 2009. Available at: www.nice.org.uk/guidance/PH21
  27. NICE website. Quality standard for antenatal care. Quality Standard 22. www.nice.org.uk/guidance/QS22 (accessed 25 September 2014).
  28. NICE website. Quality standard for patient experience in adult NHS services. Quality Standard 15. www.nice.org.uk/guidance/QS15 (accessed 25 September 2014).
  29. NICE website. Quality standard for drug use disorders. NICE Quality Standard 23. www.nice.org.uk/guidance/QS23 (accessed 25 September 2014).
  30. Department of Health. Hepatitis B antenatal screening and new-born immunisation programme: best practice guidance. London: DH, 2011. Available at www.gov.uk/government/uploads/system/uploads/attachment_data/file/215622/dh_132637.pdf
  31. Royal College of General Practitioners. Hepatitis B and C: Detection, diagnosis and management. London: RCGP, 2014. Available at: www.rcgp.org.uk/courses-and-events/online-learning/ole/hepatitis-b-and-c.aspx

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