Testing for hepatitis C virus (HCV) in patients at high risk of infection

Hepatitis C infection occurs through exposure to infected blood or body fluids. The majority of newly acquired infections in New Zealand are from injectable drug use.

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Key Practice Points

  • Identify patients with HCV infection by testing those at high risk
  • Testing begins with serology for anti-HCV antibodies
  • Positive serology must be followed by an HCV RNA assay or HCV core antigen assay
  • HCV RNA quantitation and HCV genotype testing are no longer required

Hepatitis C infection occurs through exposure to infected blood or body fluids.1 The majority of newly acquired infections in New Zealand are from injectable drug use.2 Promoting the use of clean needles for people using injectable drugs is important to reduce new infections. If people using injectable drugs are not already receiving assistance, they should be referred to community alcohol and drug services (CADS) and a local needle exchange service.

For a list of facilities involved in the New Zealand needle exchange programme, see: www.nznep.org.nz/outlets

Some patients with hepatitis C will have acquired iatrogenic infection from contaminated blood products, used in New Zealand prior to July 1992. Others may have become infected following medical or dental procedures, particularly if these were performed in countries with high HCV prevalence and/or poor infection control procedures.1, 3 Regions with high HCV prevalence include Eastern Europe, the Middle East, North Africa, Western and Central Sub-Saharan Africa, Central Asia and the Indian subcontinent.1, 3 People who have been incarcerated are also at high risk, due to the prevalence of HCV in the prison population and the use of potentially contaminated tattooing equipment. Sexual transmission plays a minor role in the spread of hepatitis C and the risk is greatest for men who have sex with men, heterosexuals with multiple partners and sex workers, especially in association with injectable drug use.4

People cannot develop immunity to HCV. Therefore, anyone who has eradicated HCV infection either spontaneously or following antiviral treatment may be re-infected.

Initial infection is usually asymptomatic

The majority of people who contract HCV are asymptomatic in the acute stages of infection with only 25–30% of people noticing symptoms.5 The symptoms of acute HCV infection are nonspecific and include:6

  • Fatigue
  • Nausea
  • Abdominal pain
  • Muscle aches
  • Jaundice

Substantially elevated alanine aminotransferase (ALT) levels, e.g. greater than ten times the upper limit of normal, occur two to eight weeks after infection.7 These levels typically spontaneously decrease to within normal limits within three to six months.8 Acute HCV infection is a Notifiable disease.

Viral clearance without treatment is possible

It is estimated that 20–25% of people infected with HCV clear the virus without medical intervention.1 Females, younger patients, and patients who develop symptoms, such as jaundice, are more likely to achieve spontaneous viral clearance.1 Patients of Polynesian and Asian ethnicity are also more likely to achieve clearance due to genetic differences associated with higher rates of spontaneous viral clearance.9, 10

The majority of patients develop long-term infection

Approximately three out of four people infected develop long-term HCV infection, placing them at increased risk of hepatic complications and making transmission of the virus more likely. Due to the slow disease process many people will be unaware of the infection. Liver function tests may be persistently normal in more than one-quarter of people with chronic HCV infection.11 People who present with symptoms of liver disease may have acquired HCV at a younger age, and the source of infection may never be identified.

In people with long-term HCV infection the risk of cirrhosis increases with the duration of infection; 20–30% of patients develop cirrhosis after 20–30 years with 2–4% of these people per year developing hepatocellular carcinoma.1, 3

Identify patients who are most likely to have been infected with HCV through their personal and maternal history. The majority of people with chronic HCV infection in New Zealand have used injectable drugs.12

Risk factors for HCV infection include:1, 3, 13

  • Injectable drug use
  • Receiving a blood transfusion in New Zealand prior to July, 1992
  • Migration from or receiving health care in a region with high HCV prevalence
  • Time spent in prison
  • A tattoo, body piercing or alteration, e.g. scarification, which was not performed in a licenced premises within New Zealand, i.e. either performed in prison or in a country with a high prevalence of HCV
  • History of acute hepatitis, jaundice, or abnormal liver function
  • Being born to an HCV infected mother; mother to infant transmission occurs in approximately 5% of infected mothers14

It is recommended that all patients with these risk factors undergo testing for HCV infection.1 In practice, a reasonable approach is to offer HCV testing to patients with risk factors and ensure that new patients with risk factors are identified on enrolment.

For further information on strategies for identifying patients at risk and discussing HCV testing, see: www.bpac.org.nz/2017/hepc.aspx

The HCV testing process

Diagnosing HCV infection typically involves two tests; some laboratories may perform these as reflex tests:

  1. Screening test for HCV exposure: anti-HCV antibodies
  2. Confirmatory test for active HCV infection. Either*:
    • a. HCV RNA assay
    • OR
    • b. HCV core antigen assay

* Some laboratories may perform these as reflex tests
Anticipated to be available at some stage during 2019

Additional tests for other forms of hepatitis and HIV are generally requested at the same time.

For further information on the diagnosis and management of hepatitis B, see: www.bpac.org.nz/2018/hepb.aspx

Testing starts with HCV serology

Serology is the first-line test for investigating HCV infection in the majority of patients (Figure 1). Antibodies to HCV may take up to six months to develop and only 50% of patients are likely to have positive serology during the acute stage of infection; delayed testing may be appropriate for these patients.15 Discuss the limitations of testing with patients with ongoing risk of infection, e.g. current injectable drug users, and the delay between infection and HCV antibody production.

Negative serology indicates the absence of HCV infection, unless the patient is immunosuppressed or they have an acute HCV infection.

Positive serology indicates either a current or previous HCV infection, or a false positive, and must be followed by an HCV RNA or HCV core antigen assay to determine if the patient has a current infection (see below).

* Anticipated to be available at some stage during 2019

Figure 1: Testing patients for HCV infection.22, 23

HCV serology is not diagnostic for hepatitis C

Serology tests have a high sensitivity and specificity, although false positive results do occur. The proportion of false positive results depends on the background prevalence of hepatitis C; in populations with a low prevalence, false positive results can account for up to 35% of positive results.16 Testing patients without risk factors for HCV infection is therefore not recommended. Serology must be followed by HCV RNA testing to determine if the infection is current.16 If a patient has a positive serology and a negative HCV RNA or HCV core antigen test they are not currently infected and do not require treatment.

False negatives are uncommon: it is estimated that 99% of patients with a long-term infection and detectable HCV RNA or HCV core antigen will test positive for anti-HCV antibodies.17

A positive HCV RNA assay or HCV core antigen assay confirms current infection

HCV RNA detected through a polymerase chain reaction assay detects and quantifies viral RNA (Figure 1). In acute infection, HCV RNA can be detected within one to two weeks of exposure and levels increase two to eight weeks after infection.7

It is anticipated that an alternative test for current infection, the HCV core antigen assay, will become available at some stage during 2019. These will be performed as reflex tests in patients who test positive for anti-HCV antibodies. The HCV core antigen assay detects viral antigens produced during HCV replication.18 It is less sensitive than an HCV RNA assay and may not detect very early HCV infection.19 However, a positive HCV core antigen test can reliably confirm established chronic infection, with a sensitivity of 93.4% and specificity of 98.8% compared to an HCV RNA assay.20 As is the case with the HCV RNA assay, a negative HCV core antigen assay at 12 weeks after completion of antiviral therapy confirms successful HCV eradication.20, 21

A positive HCV RNA or HCV core antigen result indicates current infection, either acute or long-term (see: “Conservative management is generally appropriate for acute infection”). Patients should be informed of positive results in person and counselled about transmission prevention (see “Advice for patients to reduce the risk of HCV transmission”).

A negative HCV RNA or HCV core antigen assay indicates the patient does not have current infection and does not require treatment. For patients diagnosed during the acute stage of infection, repeat testing after three months is recommended to confirm the negative result.15

HCV genotyping is no longer required

Previously, HCV genotyping was required to determine eligibility for treatment, as Viekira Pak regimens are only effective against HCV genotypes 1 and 4. From 1 February, 2019, genotype testing is no longer required as glecaprevir + pibrentasvir (Maviret) is effective against all HCV genotypes.6

Published: 30 January 2019 | Updated: 22 February 2019

22 February 2019 Footnote added to ‘HCV core antigen assay’ test; repeat testing after a negative HCV RNA assay clarified in Figure 1.


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