• Antenatal screening for hepatitis B is routinely offered to all pregnant women.
• Consider opportunistic screening of people at high risk of hepatitis B, particularly for those who:
• Are more likely to have been exposed to hepatitis B (such as immigrants from areas with a high prevalence, injecting drug users, and sex workers).
• Have been sexually assaulted.
• Have sustained a needlestick injury.
• Are HIV-positive.
• In people at high risk of hepatitis B, consider offering the first dose of hepatitis B vaccine and taking blood for serology testing at the same appointment.
• If serology tests later show immunity, do not give the remaining doses of vaccine.

These recommendations are based on the United Kingdom national guideline on the management of the viral hepatitides A, B, and C [BASHH, 2008] and are consistent with advice from other guidelines and CKS expert reviewers.

• CKS does not recommend waiting for the serology results prior to vaccinating high-risk people on the basis of urgency, opportunity, and cost (recommendation from CKS expert reviewers). People at a higher risk of prior infection should be tested alongside the first dose of vaccine, both to look for chronic disease and to look for immunity. Testing for previous exposure is only cost-effective if seroprevalence in the target population is sufficiently high. This is not usually the case in UK populations at normal risk of hepatitis B.
• The recommendation to screen immigrants from countries with a high prevalence of hepatitis B when they register with a general practice is based on expert opinion from the British Liver Trust [British Liver Trust, 2009].

• Screening for hepatitis B usually involves testing for hepatitis B surface antigen (HBsAg) or for antibody to hepatitis B core antigen (anti-HBc), but laboratory policy varies.
• The detection of HBsAg indicates acute hepatitis B or chronic hepatitis B infection.
• The detection of anti-HBc indicates current or past hepatitis B infection.
• Provide full details to the laboratory. A request for 'hepatitis screen' or 'hepatitis serology' alone is likely to be inadequate. The following information should be included to allow the laboratory to select the appropriate tests:
• The person's vaccination status.
• Whether the test is for past exposure or response to vaccination.
• Whether or not acute hepatitis is suspected.
• If the person is immunocompromised (when hepatitis B virus [HBV]-DNA may be of more use).

This information is from a guideline published by the Royal College of General Practitioners [RCGP, 2005], the United Kingdom national guideline on the management of the viral hepatitides A, B, and C [BASHH, 2008], and expert opinion from a review article [Cooke et al, 2010].

Choice of test

• CKS expert reviewers differed in their opinion on the specific serology tests to request; this clearly depends on the clinical situation and local laboratory policy. It is essential to provide full detailed clinical information when requesting hepatitis serology as laboratories vary in the tests performed.
• Request for a 'hepatitis B screen' will often result in only the HBsAg test being done. Unless acute hepatitis is suspected, this may be all that is required. However, several CKS expert reviewers noted that testing for both HBsAg and anti-HBc is preferable. Whilst some laboratories routinely test for both HBsAg and anti-HBc, others may not.

• Acute hepatitis B cannot easily be distinguished from other forms of acute hepatitis either by history or examination, or through routine biochemistry.
• Acute hepatitis B:
• Is asymptomatic in around 50% of adults and in most infants and young children.
• Has an incubation period of generally 60–90 days (but this ranges from 40–160 days).
• Can present as a serum sickness-like prodromal illness (in 10% of people).
• Fever, arthralgia, or a rash may appear about 2 weeks prior to the onset of jaundice; such symptoms usually subside when the jaundice appears.
• Often presents with symptoms that are ill-defined and have an insidious onset. These include:
• Nonspecific malaise — which may be profound, with disinclination to smoke or to drink alcohol.
• Fever — if present, it is usually mild.
• Nausea and poor appetite.
• Pain in the right upper abdominal quadrant.
• Jaundice — occurs in only about 10% of younger children and 30–50% of adults. Urine becomes darker, and the stools paler, in cholestasis.
• Fulminant hepatitis — occurs in less than 1% of people.
• Extrahepatic manifestations — such as glomerulonephritis, vasculitis, and polyarteritis.
• In the absence of clinical features of hepatitis, suspect acute hepatitis B if the person has:
• Altered liver function tests.
• In acute hepatitis B, ALT (alanine transaminase) and AST (aspartate transaminase) levels typically reach 1000–2000 IU/L (with ALT being higher than AST).
• Characteristic serological markers of acute hepatitis B infection.
• If hepatitis B is suspected, confirm the diagnosis by serology.

• Extrahepatic manifestations may be seen in both acute and chronic hepatitis B. They are thought to be mediated by circulating immune complexes.
• Polyarteritis nodosa (PAN) is a vasculitis of small-to-medium-size arteries, which can present with fever, rash, hypertension, eosinophilia, abdominal pain, renal disease, and polyarthritis.
• Papular acrodermatitis (Gianotti–Crosti syndrome) is a rare but characteristic rash affecting children. It consists of flat, erythematous, and papular eruptions (2–3 mm) localized to the face and extremities. It persists for 15–20 days.
• Membranous glomerulonephritis is rare. It presents with proteinuria and nephrotic syndrome. It is more common in children but progression to renal failure is more common in adults.

[James-Koziel and Thio, 2009]

This information is based on the United Kingdom national guideline on the management of the viral hepatitides A, B, and C [BASHH, 2008], guidance from the Health Protection Authority [HPA, 2010a], Immunisation against infectious disease (the 'Green Book') [DH, 2009a], information published by the British Liver Trust [British Liver Trust, 2009], and an expert review article [James-Koziel and Thio, 2009].

• Symptoms and signs of chronic hepatitis B infection are often absent.
• When present, symptoms are usually mild and non-specific.
• Fatigue or loss of appetite are common.
• Nausea, discomfort in the right upper abdominal quadrant, myalgia, and arthralgia also occur.
• Occasionally, chronic hepatitis B presents with extrahepatic manifestations (such as glomerulonephritis, vasculitis, and polyarteritis).
• Signs of chronic liver disease may develop in the longer term.
• These include spider naevi, finger clubbing, jaundice, and hepatosplenomegaly.
• If advanced cirrhosis develops, there may be:
• Easy bruising.
• Oedema and abdominal swelling (ascites).
• Liver flap and encephalopathy.
• Progressive weight loss, muscle wasting, and weakness.
• Progressive jaundice.
• People with chronic hepatitis B may also be identified:
• Following screening tests for people at high risk.
• Through follow up, after a diagnosis of acute hepatitis B.
• Because of abnormal liver function tests.
• The most common abnormalities are mild increases in levels of ALT (alanine transaminase) and AST (aspartate transaminase).
• ALT levels may be only mildly elevated (less than 100 IU/L); the progression to chronic infection is indicated when this persists for more than 6 months after acute hepatitis B.
• Alkaline phosphatase levels tend to be normal (or nearly normal).
• Bilirubin and albumin levels, and prothrombin time, are usually normal (unless liver disease is severe and advanced).

This information is from the United Kingdom national guideline on the management of the viral hepatitides A, B, and C [BASHH, 2008], the Health Protection Agency [HPA, 2010a], Immunisation against infectious disease (the 'Green Book') [DH, 2009a], information published by the British Liver Trust [British Liver Trust, 2009], and textbooks [Dienstag, 2009; James-Koziel and Thio, 2009].

• Hepatitis B surface antigen (HBsAg) is the first biochemical marker to rise in people with hepatitis B.
• It rises during the incubation period, and may be cleared early in the course of the disease. It is undetectable in 10% of people by the time the test is performed.
• Chronic hepatitis B occurs when HBsAg persists in the serum for 6 months or longer.
• Hepatitis B e-antigen (HBeAg) and hepatitis B virus-DNA (HBV-DNA) are detectable around the same time as, or shortly after, HBsAg.
• Disappearance of HBeAg, development of antibodies to HBeAg (anti-HBe), and a decline in HBV-DNA indicates control of viral replication and predicts resolution of acute hepatitis B.
• Persistence of HBsAg, HBeAg, and HBV-DNA indicates possible progression to chronic hepatitis B.
• People with chronic hepatitis B tend to be more infectious if HBeAg is also detected. If HBeAg has been cleared, anti-HBe is usually detected, and infectivity is lower.
• High levels of HBV-DNA may indicate a greater risk of progression to cirrhosis and hepatocellular cancer.
• Immunoglobulin M (IgM) antibody to hepatitis B core antigen (anti-HBc) is the first antibody to arise after infection.
• IgM anti-HBc indicates infection within the last 6 months.
• It usually appears within 1 month of HBsAg, and 1–2 weeks before the increase in alanine transaminase (ALT).
• Its presence generally distinguishes acute disease from an exacerbation.
• It is usually replaced gradually by immunoglobulin G (IgG) anti-HBc.
• IgG anti-HBc generally persists for life and indicates infection at some time in the past.
• Antibody to HBsAg (anti-HBs) develops during convalescence following the disappearance of HBsAg.
• Anti-HBs indicates recovery from hepatitis B. However, complex interactions may allow coexistence of HBsAg and anti-HBs in up to 25% of inactive HBsAg carriers.
• Anti-HBs persists for life.
• Anti-HBs without anti-HBc is a marker of immunization.
• For a summary of this information in table format, see Interpretation of hepatitis B serology tests (table).

This information is based on the United Kingdom national guideline on the management of the viral hepatitides A, B, and C [BASHH, 2008], guidance from the Health Protection Agency [HPA, 2010a], Immunisation against infectious disease (the 'Green Book') [DH, 2009a], information published by the British Liver Trust [British Liver Trust, 2009], and an expert review article [James-Koziel and Thio, 2009].

• Diagnosis of acute hepatitis B is made by detection of:
• Hepatitis B surface antigen (HBsAg), and
• Immunoglobulin M antibody to hepatitis B core antigen (IgM anti-HBc).
• Chronic hepatitis B is defined as:
• HBsAg-positive on two occasions at least 6 months apart, or persistence of HBsAg for at least 6 months following acute infection.
• HBsAg-positive plus anti-HBc IgM-negative plus anti-HBc-positive.

Information on confirmation of the diagnosis is based on A professional's guide to hepatitis B [British Liver Trust, 2009] and Immunisation against infectious diseases (the 'Green Book') [DH, 2009a]. The Health Protection Agency's case definitions for chronic hepatitis are defined in Standards for local surveillance and follow up of hepatitis B and C [HPA, 2006].

• The differential diagnosis of hepatitis B includes:
• Alcoholic liver disease.
• Non-alcoholic fatty liver disease.
• Autoimmune hepatitis.
• Metabolic and genetic disorders (such as Wilson's disease, hereditary haemochromatosis, alpha₁ antitrypsin deficiency).
• Drug-induced liver disease.
• Granulomatous disorders.
• Hepatitis caused by other viruses (such as hepatitis A, C, and D).

Information about the differential diagnosis of hepatitis B is from a textbook [Dienstag, 2009].