Recent updates to NICE guidance have provided clarity on how people with chronic hepatitis B should be assessed, treated and monitored after treatment
The management of chronic hepatitis B is complex due to its four disease stages. Monitoring is often required to inform future management; not all patients will require interventions. The long-term goals of treatment are to halt disease progression and to prevent cirrhosis, hepatocellular carcinoma and liver failure.A number of guidelines are available, including those issued by the European Association for the Study of Liver Disease and recently published National Institute of Health and Care Excellence guidelines. This article, the second in a two-part series, discusses the assessment and management of chronic hepatitis B in light of recent guidelines and the role of nurses in caring for patients with CHB. Part 1 looked at the prevalence and pathophysiology of chronic hepatitis B, recommendations for screening high-risk groups and immunisation.
Citation: Oakes K (2014) Chronic hepatitis B 2: management of chronic hepatitis B virus. Nursing Times; 110: 8, 20-24.
Author: Kathryn Oakes is viral hepatitis clinical nurse specialists team lead at King’s College Hospital, London.
- This article has been double-blind peer reviewed
- Scroll down to read the article or download a print-friendly PDF including any tables and figures
- Read part 1 of this series here
Hepatitis B is considered to be a dynamic disease as it can change over time and is thought to have four phases (Oakes, 2014):
- Immune tolerant phase;
- Immune clearance phase (immuno-active);
- Inactive carrier phase (immune control);
- Reactivation phase.
The management of chronic hepatitis B (CHB) is complex and a period of monitoring is often needed to inform the management of patients; those with inactive disease require lifelong monitoring.
A number of guidelines are available on the management of CHB, including the European Association for the Study of Liver Disease clinical practice guidelines (EASL, 2012) and the American Association for the Study of Liver Disease practice guidelines for the management of HBV (Lok and McMahon, 2009). Specialist centres in the UK have developed local guidance, while the National Institute for Health and Care Excellence recently published guidance on the diagnosis and management of CHB in children, young people and adults (NICE, 2013).
NICE (2013) recommends that all laboratory investigations and the initial liver ultrasound are carried out in primary care and the results sent to specialist centres with the referral. This differs from the existing model where the entire assessment takes place in hospital settings, usually at specialist centres.
All patients with CHB should have a thorough initial assessment. A clinical history should be taken that includes ethnicity, place of birth, risk factors for acquiring the hepatitis B virus (HBV), family history of CHB or hepatocellular carcinoma (HCC), any previous HBV medication and any factors that could influence disease progression (Lee et al, 2010).
A physical examination should be carried out to look for signs and symptoms of liver disease and all patients should have a baseline liver ultrasound. Laboratory investigations to check for other forms of liver disease or bloodborne viruses should be part of the initial assessment and include HBV serology (including genotype), assessment of liver enzymes and hepatic function, metabolic liver disease screen, renal and bone profile, full blood count and INR (international normalised ratio), alpha-fetoprotein and co-infections with HIV, hepatitis C virus or hepatitis D virus (delta virus) (B Positive, 2008).
HBV can change over time, as some patients move through all four phases (Oakes, 2014). Those with HBeAg positive disease can seroconvert; this is where HBeAg is lost and HBeAb (the antibody to HBeAg) is formed. During some phases of CHB - such as in the immunoactive phase - levels of HBV DNA and liver enzyme alanine aminotransferase (ALT) fluctuate, so sequential measurements should be taken to inform disease management.
EASL (2012) and NICE (2013) have made recommendations for monitoring patients in the immune tolerant and immune control phases (Table 1).
Liver fibrosis assessment is essential when considering whether to start antiviral treatment of active CHB. There are two modalities - liver biopsy and the Fibroscan.
Liver biopsies are considered the gold standard in assessing fibrosis and necro-inflammation (inflammatory activity) levels; they may detect other forms of liver diseases concomitant with the HBV (Mani and Kleiner, 2009). However, the procedure is painful and invasive and has the potential for life-threatening complications and sampling errors (Maimone et al, 2009).
A number of scoring systems are used to interpret liver biopsy results, including the Metavir (fibrosis scale 0-4 and inflammatory scale 0-3) and Ishak scores (fibrosis score 0-6 and NI scale 0-18). The levels of fibrosis and necro-inflammation increase with rising scale scores in both systems.
The Fibroscan (transient elastography) is being increasingly used as an alternative to liver biopsy or to help decide whether a patient needs a liver biopsy. It measures liver elasticity, giving a liver stiffness measurement (LSM) in kilopascals (kPa), which indicates the level of liver fibrosis. Fibroscans are quick to perform, convenient for patients, give instant results and are non-invasive, painless and highly accurate in CHB patients with severe fibrosis and cirrhosis (Marcellin et al, 2009).
However, Fibroscan readings increase with necro-inflammatory activity, in acute hepatitis, and during biochemical flares of hepatitis and cirrhosis (Wang et al, 2009), and may not be accurate in these circumstances. Severe obesity can affect readings, even with the use of an XL probe (Myers et al, 2012). Fibroscans cannot be used in pregnancy, in patients with ascites or where there is any type of swelling or fluid retention in the abdominal area.
NICE (2013) recommends Fibroscan as the initial test for liver disease in adults with CHB (Table 2).
Goals of treatment
As most patients are asymptomatic, the long-term treatment goals are to stop disease progression and prevent cirrhosis, liver failure and HCC (Shamliyan et al, 2009).
HBV is difficult to eradicate because its covalently closed circular DNA (cccDNA) becomes established in hepatocyte nuclei and incorporated into the host genome (Dienstag, 2008); it is controllable rather than curable. Durable viral suppression and E antigen seroconversion (HBeAg positive patients only), normalisation of ALT and histological improvement are considered to be good treatment outcomes (Hadziyanis, 2011).
NICE (2013) does not recommend using genotype testing to determine a plan of treatment in people with CHB, contrary to previous guidelines (Table 3).
Treatment choice for CHB should be based on a medical assessment of the risks and benefits, and should take into account whether women are of childbearing age. Safety, efficacy and drug resistance need to be considered (Dusheiko, 2013). All these factors must be discussed with patients so they can make informed decisions. Some advantages of the most commonly used antiviral agents, discussed below, should also be explained.
Treatment during pregnancy
The NICE guideline (2013) recommends:
- Tenofovir is offered to pregnant women with HBV DNA levels >10 E7 IU/ml in the third trimester to reduce the risk of HBV transmission to the baby;
- HBV DNA levels should be checked two months after starting tenofovir and the ALT levels should be checked monthly after birth to detect postnatal flares;
- Treatment can be discontinued 4-12 weeks after delivery, unless the mother meets the criteria for long-term treatment;
- Mothers may breastfeed while taking antiviral therapy.
Pegylated interferon stimulates the immune system to attack the virus with the intention of making it inactive; it also has a mild antiviral action (Lau et al, 2005).
It is a fixed course but has more side- effects than oral medications, including flu-like symptoms, anorexia and weight loss, depression and bone marrow suppression (Pomfret and Wong, 2007).
Pegylated interferon is contraindicated in some patients, such as those with severe depression or uncontrolled epilepsy (Dusheiko, 2013), so patients should be fully assessed before it is considered.
In HBeAg-positive patients, pre-treatment predictors of HBeAg seroconversion and HBsAg loss include if patients have:
- Genotype A or B (rather than C or D);
- High ALT levels (greater than 2-5 times the upper limit of normal);
- Low HBV DNA levels (less than 2 x 108);
- High activity scores on liver biopsy (EASL, 2012).
There are no clear pre-treatment predictors of response in HBeAg-negative patients. See part one of this series (Oakes, 2014) for an explanation of HBeAg positive and negative status.
Pegylated interferon is administered by weekly injection for 48 weeks, and patients need to be closely monitored by a clinical nurse specialist. Those who have completed a course need to be monitored as they may respond after treatment.
Oral antiviral agents
Tenofovir (a nucleotide analogue) and entecavir (a nucleoside analogue) are safe and potent medicines with high genetic barriers to resistance. These medications are taken as a single therapy, in tablet form once daily, and interrupt the HBV lifecycle by inhibiting viral polymerase, which is essential for viral replication.
The advantages of oral agents are that they have fewer side-effects, such as headaches and occasional nausea, than pegylated interferon. However, they need to be taken for many years, if not for life.
In HBeAg-positive CHB, pre-treatment factors that may predict HBeAg seroconversion are:
- Low viral load (HBV DNA level less than 2 x 108 IU/ml);
- High serum ALT levels;
- High activity scores on liver biopsy.
HBV genotype, however, does not influence viral response (EASL, 2012).
Some renal dysfunction has been reported in patients with HIV taking tenofovir (Electronic Medicines Compendium, 2013), but this seems to be less of a problem for HBV patients (Pol and Lampertico, 2012). NICE (2013) suggests that adverse renal events may cause long-term bone fragility, but does not make any recommendations on the cost-effectiveness of routine monitoring for phosphate loss and bone disease.
Patients taking these medications need to be monitored for the long term by a nurse specialist or doctor.
Treatment response rates
Table 4 shows the response rates to entecavir, tenofovir and pegylated interferon as well as their resistance rates.
Treatment response must be evaluated at specific time points in patients taking pegylated interferon and at each clinic visit for those taking oral agents, to ensure clinical management is effective and safe.
Although cirrhosis is a risk factor for HCC, it can occur if cirrhosis is not present (Elgouhari et al, 2008). Table 5 shows the groups recommended to have routine HCC screening, 6-12 monthly liver ultrasound scans and alpha-fetoprotein measurement.
Monitoring and support
Patients receiving pegylated interferon need to be shown how to administer their injections and attend regular clinic visits (usually monthly) to collect medication and manage side-effects. Blood samples should be taken at each visit for full blood counts and biochemical profiles, with periodic thyroid function, auto-antibody and immunoglobulin tests. Serological markers should be taken before, during and after treatment.
Patients receiving oral antiviral agents need to attend every six months once they are established on treatment; blood samples should be taken to check full blood count, liver and renal profiles, and response to treatment. Adherence to medications should be checked and reinforced at each visit and advice on adherence measures should be given if needed.
HCC screening should be timed to fit in with clinic visits.
Patients living with long-term conditions are encouraged to self-manage where possible (DH, 2009). However, those with CHB often lack self-care knowledge (Lan Huong et al, 2012). All patients with CHB should receive individualised education on the following:
- Modes of HBV transmission, how to avoid onward transmission, and the need for testing and vaccination of close household contacts, sexual partners and direct family members;
- The dynamic nature of HBV meaning regular clinic visits for monitoring may be needed; how often they need to visit;
- Blood tests and their significance so patients understand the importance of attending clinic;
- The stages of CHB, its long-term effects on the liver, and that the absence of symptoms does not correlate with disease progression;
- The need for HCC screening with six-monthly liver ultrasounds and AFP measurements;
- Alcohol use, cigarettes and herbal medicines, remedies or teas - NICE (2013) recommends that other lifestyle issues, such as weight management and a healthy diet, are discussed;
- Monitoring and treatment in pregnancy and the need for babies to be vaccinated.
Patients starting treatment with pegylated interferon or oral medication, should be educated about:
- The risks and side-effects;
- Short- and long-term treatment goals, and the fact that HBV is usually controllable but not curable;
- The duration of treatment - 48 weeks for pegylated interferon and probably lifelong for oral antiviral agents;
- Pegylated interferon - collection and storage of doses, when to take them, rotation of injection sites, disposal of sharps, avoidance during pregnancy and breastfeeding, common remedies to alleviate side-effects;
- Oral antiviral agents - how often to take tablets and whether this should be with food, renal monitoring with tenofovir, adherence, resistance and advice on pregnancy or breastfeeding.
Education should use simple terminology and take into account cultural needs and religious beliefs, using an interpreter if needed. Patients should be given written information in their own language and made aware of community groups, forums or resources that may help. Patients, families and carers should be given a personalised care plan outlining proposed treatment and long-term management (NICE, 2013).
CHB management remains complex, with many areas subject to debate. The NICE guideline should be used in the context of clinician experience and the patient’s condition and wishes. New developments being trialled will add to the complexity of CHB management but will also enhance care.
A crucial, ongoing element of nurses’ roles will be to give people with CHB up-to-date information so they can make informed decisions.
NICE proposes that CHB patients’ initial investigations take place in primary care. This will require systems being put in place in the community and GPs engaging with specialist services. If this is achieved, a logical progression would be for those in the immune control phase (who make up the largest proportion of CHB patients and have a low complexity) to move towards a more community-based model of care, along with other non-complex CHB patients.
- NICE recommends initial assessments are carried out in primary care
- Patients with CHB need an initial assessment, usually followed by monitoring
- People with CHB are at risk of hepatocellular carcinoma and may need surveillance for this
- CHB is rarely cured, so goals of treatment are to halt disease progression and prevent liver failure, cirrhosis and HCC
- Nurses’ roles cover assessment, education, self-management, adherence, monitoring and providing support, advice and care
B Positive (2008) All You Wanted to Know About Hepatitis B. A Guide for Primary Health Care Providers. Australasian Society for HIV Medicine.
Brunetto MR, Lok AS (2010) New approaches to optimize treatment response in chronic Hepatitis B. Antiviral Therapy; 15: S3, 61-68.
Department of Health (2009) Your Health, Your Way - a Guide to Long Term Conditions and Self Care. London: DH.
Dienstag JL (2008) Hepatitis B virus infection. New England Journal of Medicine; 359: 14, 1486-1500.
Dusheiko G (2013) Treatment of HBeAg positive chronic hepatitis B: interferon or nucleoside analogues. Liver International; 33: 137-150.
Electronic Medicines Compendium (2013) Viread: Summary of Product Characteristics.
Elgouhari HM et al (2008) Hepatitis B virus infection: understanding its epidemiology, course, and diagnosis. Cleveland Clinical Journal of Medicine; 75: 12, 881-889.
European Association for the Study of the Liver (2012) Updated EASL clinical practice guidelines: management of chronic Hepatitis B. Journal of Hepatology; 57, 167-185.
Hadziyannis SJ (2011) Milestones and perspectives in viral hepatitis B. Liver International; Suppl 1: 129-134.
Lan Huong VT et al (2012) An analysis of self-care knowledge of hepatitis B patients. Bulletin Luxembourgeois des Questions Sociales; 29: 1, 225-236.
Lau GK et al (2005) Peginterferon alfa 2a, lamivudine and the combination for HBeAg chronic hepatitis B. New England Journal of Medicine; 352: 26, 2682-2695.
Lee H et al (2010) Management of hepatitis B virus infection. Gastroenterology Nursing; 33: 2, 120-126.
Lok SF, McMahon BJ (2009) Chronic hepatitis B 2009. American Association for the Study of Liver Disease practice guideline update. Hepatology;
Luo J et al (2013) Efficacy of entecavir treatment for up to 5 years in nucleos(t)ide-naïve chronic hepatitis B patients in real life. International Journal of Medical Sciences; 10: 4, 427-433.
Maimone S et al (2009) An evaluation of transient elastography in the discrimination of HBeAgnegative disease from inactive hepatitis B carriers. Journal of Viral Hepatitis; 16, 769–774.
Mani H, Kleiner DE (2009) Liver biopsy findings in chronic hepatitis B. Hepatology; 49: S61-S71.
Marcellin P et al (2009) Non-invasive assessment of liver fibrosis by stiffness measurement in patients with hepatitis B. Liver International; 29: 2, 242-247.
Myers RP et al (2012) Discordance in fibrosis staging between liver biopsy and transient elastography using the FibroScan XL probe. Journal of Hepatology; 56: 3, 564-570.
National Institute for Health and Care Excellence (2013) Hepatitis B (Chronic). Diagnosis and Management of Chronic Hepatitis B in Children, Young People and Adults. London: NICE.
National Institute for Health and Care Excellence (2009) Medicines Adherence: Involving Patients in Decisions about Prescribed Medicines and Supporting Adherence. London: NICE.
Negro F (2011) Management of chronic hepatitis B: an update. Swiss Medical Weekly; 141: w13264.
Oakes K (2014) Hepatitis B: prevalence and pathophysiology. Nursing Times; 110, 7, 12-16.
Pol S, Lampertico P (2012) First-line treatment of chronic hepatitis B with entecavir or tenofovir in ‘real-life’ settings: from clinical trials to clinical practice. Journal of Viral Hepatitis; 19: 6, 377–386.
Pomfret T, Wong J (2007) Pharmacologic management of chronic hepatitis B. Formulary Watch; 42: 429-438.
Shamliyan TA et al (2009) Antiviral therapy for adults with chronic hepatitis B: a systematic review for a National Institutes of Health consensus development conference. Annals of Internal Medicine; 150: 2, 111-124.
Wang JH et al (2009) Fibroscan and ultrasonography in the prediction of hepatic fibrosis in patients with chronic viral hepatitis. Journal of Gastroenterology; 44, 439-446.
Yuen MF, Lai CL (2011) Treatment of chronic hepatitis B: evolution over two decades. Journal of Gastroenterology and Hepatology; 26: Suppl. 1; 138–143.