Definitions for the level of evidence (I-IV) and grade of recommendation (A-C) are provided at the end of the "Major Recommendations" field.
Screening/Diagnosis
Hepatitis A Virus (HAV)
- Diagnostic tests for HAV are recommended in anyone presenting with an acute illness or raised transaminase levels, suggesting acute hepatitis and in contacts of known cases (sexual, household or other close contact) (Evidence Level II).
- Screening of asymptomatic sexually transmitted disease (STD) clinic attendees is recommended to ascertain their immune status only if they meet the criteria for hepatitis A vaccination (see the National Guideline Clearinghouse [NGC] summary of the British Association for Sexual Health and HIV [BASHH] National Guideline on Management of the Viral Hepatitides A, B & C) which includes homosexual men in regions where an outbreak of hepatitis A has been reported, injecting drug users, and patients with chronic hepatitis B or C, or other causes of chronic liver disease (Evidence Level III).
Hepatitis B Virus (HBV)
- Diagnostic tests for HBV are recommended in anyone presenting with suspected acute hepatitis and in those with symptoms or signs of chronic liver disease, or abnormal liver function tests (LFTs) consistent with acute or chronic hepatitis (Evidence Level II).
- Screening of asymptomatic STD clinic attendees is recommended if they fall into one of the groups at increased risk of hepatitis B and who should be given vaccine if still susceptible. The testing strategy used should identify both those who are already immune to infection and those who are currently infected (most will be chronic carriers). Those who should be screened include homosexual men or their contacts, sex workers or their contacts, intravenous drug users or their contacts, recipients of blood/blood products, needlestick recipients, sexual assault victims, human immunodeficiency virus (HIV)-positive people and sexual partners of hepatitis B surface antigen (HBsAg)-positive people (Evidence Level II), and people from areas where hepatitis B is endemic.
- Screening of patients who have been born, raised or otherwise resident in endemic countries and travellers who have had sexual contacts in endemic countries, is also recommended to identify those who are currently infected and may be at risk of transmitting infection to others (those who are still susceptible should be given vaccine only if they are at future risk of infection) (Evidence Level II).
Hepatitis C Virus (HCV)
- Diagnostic tests for HCV are recommended in anyone presenting with suspected acute hepatitis, and in those with symptoms or signs of chronic liver disease, or abnormal LFTs consistent with acute or chronic hepatitis (Evidence Level II).
- Screening of asymptomatic STD clinic attendees is recommended if they fall into one of the groups at increased risk which includes intravenous drug users, recipients of blood/blood products, needlestick recipients, HIV-positive people and sexual partners of HCV-positive people (Evidence Level II).
Recommended Tests
NOTE: For simplicity the following recommendations refer to tests, such as enzyme-linked immunosorbent assay (ELISA) or deoxyribonucleic acid (DNA) amplification which are all, unless otherwise stated, conducted on blood samples. Most commercial serological assays for hepatitis virus infections can be used with either serum or plasma. Local protocols should be agreed with relevant laboratory departments.
Hepatitis A
- To diagnose suspected acute hepatitis: ELISA for anti-HAV immunoglobulin M (IgM) (detectable at or before the onset of symptoms and persists for up to six months) (Evidence Level II).
- To determine if immune to infection: ELISA for anti-HAV (total antibody - standard tests detect both IgM and IgG antibody) (Evidence Level II).
- Sensitivities and specificities approach 100% (Evidence Level II).
- Assays for salivary samples exist but are not generally available for routine use. They have a sensitivity of about 80% for IgA (Evidence Level II).
Hepatitis B
- To diagnose suspected acute hepatitis: ELISA for HBsAg and IgM anti-hepatitis B core (anti-HBc) antibody. If HBsAg-positive, proceed to hepatitis B 'e' antigen (HBeAg) and antibody (HBeAb) (Evidence Level II).
- Screening in asymptomatic patients may include tests for HBsAg, anti-HBc and anti-HBs on all samples, or may follow a sequential testing algorithm (Evidence Level II). (The flow charts in the original guideline document show algorithms starting with anti-HBc or HBsAg).
- Testing for anti-HBs alone prior to vaccination may also be considered, but must be followed by serological investigation of any patient who remains anti-HBs-negative post-vaccine, because they may already be HBsAg-positive. Testing for anti-HBc antibody and anti-HBs prior to vaccination may also be considered (Evidence Level II).
- Assays for anti-HBc and HBsAg in saliva samples have been used for surveillance and research purposes but are not currently available commercially for diagnostic use (Evidence Level II).
Hepatitis C
- To diagnose suspected acute hepatitis C: serum anti-HCV by second or third generation ELISA or other immunoassays (e.g., chemiluminescence) (Evidence Level II).
- Different strategies exist to confirm a positive result. These include a recombinant immunoblot assay (RIBA), using another ELISA, or proceeding directly to an assay for HCV-RNA (Evidence Level II). Seroconversion for HCV antibody may take 3 months so antibody tests may give negative results when a patient presents with acute hepatitis (Evidence Level II). Detection of HCV-RNA by reverse-transcriptase polymerase chain reaction (RT-PCR) or another genome amplification assay will establish or exclude the diagnosis at this time (Evidence Level II). HCV-RNA can be detected as early as two weeks after infection. An HCV-antigen ELISA can be used to diagnose acute infection in HCV-antibody negative cases, but is not as sensitive as genome detection (Evidence Level II).
- HCV-RNA detection should be repeated 6 months after acute hepatitis C to confirm whether the infection has become chronic (Evidence Level II).
- Screening in asymptomatic patients: As for acute infection but test all patients with detectable HCV-antibody for HCV-RNA, to confirm persistent viral replication (Evidence Level II). Antibody-negative patients do not require further testing unless recent infection is suspected, or there is a strong suspicion of infection in an immunocompromised patient in whom persistent infection has occasionally been reported without detectable antibody (Evidence Level III).
Recommended Samples for Testing
Serum or plasma
Factors Which Alter Tests Recommended (see flow charts in the original guideline document)
- Hepatitis A: Some clinics do not test for anti-HAV in patients who are being considered for vaccination. This may be more cost-effective depending upon the age and risk group, but the additional cost may be small if, for example, HAV testing is carried out at the same time as HBV screening (Evidence Level III).
- Hepatitis B: Serum HBV-DNA may be detectable in patients with anti-HBc but without detectable HBsAg. In patients with abnormal LFTs other causes should be excluded before attributing liver disease to HBV infection in such cases (Evidence Level II). Some patients have detectable anti-HBc but neither anti-HBs nor HBsAg are detectable. These patients should be considered immune (Evidence Level I).
- Hepatitis C: In patients with abnormal LFTs serum HCV-RNA may be the only test that is positive during acute HCV infection, or rarely in immunosuppressed patients (see above) (Evidence Level II).
Sexual History
No change
Risk Groups
- Homosexual men – no change
- Sex workers – no change
- Young patients – no change
- Other groups:
- Pregnant women – no change
- Patients who are known contacts – tests as for suspected acute hepatitis
Recommendations for Frequency of Repeat Testing in an Asymptomatic Patient
- The frequency of testing depends on the history of sexual exposure and number of sexual partners. However, in the case of hepatitis A and B, once the patient has completed a course of vaccination no further repeat testing is required.
- For those at continuing risk and who have not received a course of vaccination, the following is recommended:
- Hepatitis A:
- No routine repeat screening (Evidence Level IV)
- If a previously non-immune homosexual man gives a history of contact with a known case of hepatitis A, post-exposure prophylaxis with vaccine (and possibly immunoglobulin if over 50 years old, immunocompromised, or with co-existing liver disease) should be offered as soon as possible (Evidence Level II). Prophylaxis needs to be given within 1 to 2 weeks of exposure, although immunoglobulin may be of additional value for up to 2 to 3 weeks (Evidence Level II). Screening for anti-HAV should be offered at the same time as prophylaxis with further tests if indicated clinically (Evidence Level IV).
- Hepatitis B:
- If a previously non-immune person gives a history of unprotected anal or vaginal sex with a known case of infectious hepatitis B, post-exposure prophylaxis with vaccine should be offered as soon as possible (if less than six weeks post exposure) (Evidence Level II) and screening repeated and again at three months post-exposure. Hepatitis B specific immunoglobulin should only be given if within 72 hours of first exposure (Evidence Level II).
- Otherwise repeat screening at yearly intervals if risk behaviour continues (Evidence Level IV).
- Hepatitis C:
- The rate of seroconversion after unprotected vaginal or anal sex is about two percent per year if neither partner is HIV-positive but the risk rises to over ten percent if there is HIV infection in either partner (Evidence Level II). Repeat screening should be offered to contacts with an HCV-infected partner who continues to be exposed to infection. The optimum frequency has not been defined but may be every 6 to 12 months (Evidence Level IV).
- Repeat screening of others considered to be at risk, as listed above may be offered. No frequency of screening has been defined, but annual testing may be considered (Evidence Level IV).
- There is value in screening at 6 and 12 weeks using an HCV-RNA assay after a high-risk incident (e.g., parenteral exposure from an HCV-positive source) to detect acute infection early, when therapy may reduce the risk of ensuing chronic infection, at least in HIV-uninfected patients (Evidence Level II). Antibody tests should be repeated at 3, 6 and 12 months (Evidence Level III).
- Patients with high-risk exposures to any of these viruses should be informed about the symptoms of acute hepatitis and encouraged to seek advice immediately if these develop.
Recommendation for Test of Cure
- Not relevant for these infections.
- Patients with newly diagnosed infection due to HBV or HCV should have serological markers of infection (HBsAg or HCV-RNA) measured three and six months later to establish whether the infection has become chronic (Evidence Level II).
- Serological follow-up after antiviral therapy is beyond the scope of this guideline.
Definitions:
Levels of Evidence
Ia: Evidence obtained from meta-analysis of randomised controlled trials
Ib: Evidence obtained from at least one randomised controlled trial
IIa: Evidence obtained from at least one well designed controlled study without randomisation
IIb: Evidence obtained from at least one other type of well designed quasi-experimental study
III: Evidence obtained from well designed non-experimental descriptive studies
IV: Evidence obtained from expert committee reports or opinions and/or clinical experience of respected authorities
Grading of Recommendations
- Evidence at level Ia or Ib
- Evidence at level IIa, IIb, or III
- Evidence at level IV
